Disposable thermal in-vitro diagnostic apparatus and method of conducting an in-vitro diagnostic test

ABSTRACT

A portable, disposable in-vitro diagnostic apparatus and method of performing an in-vitro diagnostic test is provided. The apparatus includes a body configured to be hand held. The body has a reaction medium supply chamber configured in selective fluid communication with a reaction chamber via a fluid conveying channel. The reaction chamber is located beneath a sample reaction chamber. The reaction medium supply chamber contains a reaction fluid therein and the reaction chamber contains a thermal reaction medium therein. The reaction fluid is selectively reactive with the thermal reaction medium to produce one of an endothermic or exothermic reaction beneath the sample reaction chamber.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application Ser.No. 61/619,406, filed Apr. 2, 2012, which is incorporated herein byreference in its entirety.

BACKGROUND

1. Technical Field

This invention relates generally to in-vitro diagnostics, and moreparticularly to apparatus and methods for conducting thermallycontrolled in-vitro diagnostics.

2. Related Art

Biological diagnostic tests are a fundamental component in the processof determining the state or condition of a biological environment. Theseenvironments include, but are not limited to, human healthcare,agriculture, live stock management, municipal systems management, andnational defense. Molecular tests that utilize nucleic acid detectionprovide an incredibly competitive level of specificity, sensitivity, andrapid timing from sampling to result. Nearly all nucleic acid detectionapproaches require signal amplification, such as Polymerase ChainReaction (PCR), to generate detectable amounts of the targeted nucleicacid segment. Traditional mechanisms used in nucleic acid detectiontests requiring PCR utilize high powered, immobile, non-disposableequipment to achieve large temperature gradients with high resolution.Although, these mechanism prove useful to obtain the test resultsdesired, they are costly and are limited to use in fixed locations,given they require large, immobile equipment.

An assay is a sequence of steps or procedures used measure the presenceor absence of a substance in a sample, the amount of a substance in asample, or the characteristics of a sample. An example of a common pointof care assay, or an assay conducted by a layperson is a blood glucosetest. In this test, the blood is mixed with glucose oxidase, whichreacts with the glucose in the sample, creating gluconic acid, gluconicacid in turn, reacts with a chemical in the assay called ferricyanide,producing ferrocyanide. Current is passed through the ferrocyanide andthe impedance reflects the amount of glucose present.

Thermal cycling is a common method of accelerating a chemical reactionor promoting a biological event. Thermal cycling is a used to amplifysegments of nucleic acid by via PCR. As shown in FIG. 1, in an exampleof a thermal cycling process, high temperature thermal cycling is usedto physically separate two stands of a double helix DNA. This process iscommonly referred to as denaturing, wherein the linked strands of theDNA are separated into two single strands. Temperatures maintainedduring denaturing are typically in the range of 94° to 96° C. The twoseparated strands from the denatured DNA are used as templates tologarithmically replicate identical copies of the targeted segment ofDNA. Upon reducing the temperature to approximately 52° C.,synthetically designed primers bind to, or “anneal” to the template DNAstrands such that they flank both sides of a target segment of denaturedstrands of DNA. DNA Polymerase and other cofactors then cause the primerto extend fully along the denatured strands of DNA and thus, a newdouble stranded piece of DNA is generated, wherein a lower controlledtemperature in the range of 70° to 80° C. is maintained.

The thermal cycling discussed above during denaturing and DNAreplication is typically controlled in a laboratory machine. The machineincludes electrical heating and cooling elements configured inelectrical communication with thermal sensors in a closed loop controlscheme. These machines are relatively large, immobile and expensive.

SUMMARY OF THE INVENTION

A portable, disposable, low-powered thermal cycling in-vitro diagnosticapparatus is provided in accordance with one aspect of the invention.The apparatus is economical and it provides a quick, reliable andeconomical method for performing a thermally activated in-vitrodiagnostic test on a selected specimen, such as DNA, for example.Further, the apparatus automatically provides a predetermined thermalcycle over a predetermined time to allow a desired analysis of thespecimen contained within the apparatus to be performed without need ofhuman intervention. The apparatus produces exothermic and endothermicthermal energy, in a balanced and controlled environment via a chemicalreaction between reactants contained within the apparatus. The reactantsare provided and automatically combined in a predetermined manner toprovide the desired thermal cycle needed to analyze the particularspecimen. Accordingly, the apparatus in accordance with one aspect ofthe invention is wholly self-contained, and thus, is fully functional toperform the desired analysis without need of external apparatus.

In accordance with another aspect of the invention, the apparatus can beconfigured for operable attachment to an external source of power. Theexternal source of power can be provided as a hand held device that isconfigured for attachment to the in-vitro diagnostic apparatus. Theseparate source of power can be re-used, while the apparatus remainsdisposable.

In accordance with another aspect of the invention, the external energysource can be configured to produce the desired energy profile withinthe apparatus. A simple circuit may provide for intermittent, or cyclingof the energy source, resulting in a thermal cycling profile in thereaction chamber of the apparatus.

In accordance with another aspect of the invention, a portable,disposable in-vitro diagnostic apparatus includes a body configured tobe hand held. The body has a reaction medium supply chamber configuredin selective fluid communication with a reaction chamber via a fluidconveying channel. The reaction chamber is located beneath a samplereaction chamber. The reaction medium supply chamber contains a reactionfluid therein and the reaction chamber contains a thermal reactionmedium therein. The reaction fluid is selectively reactive with thethermal reaction medium to produce one of an endothermic or exothermicreaction beneath the sample reaction chamber.

In accordance with another aspect of the invention, a conductive barrierseparates the sample reaction chamber from the reaction chamber.

In accordance with another aspect of the invention, the portable,disposable in-vitro diagnostic apparatus includes an overflow chamberdownstream from the reaction chamber.

In accordance with another aspect of the invention, a rupturablemembrane selectively closes off the fluid conveying channel from thereaction medium supply chamber.

In accordance with another aspect of the invention, a self-actuatablevalve is disposed between the fluid conveying channel and the reactionchamber. The self-actuatable valve is movable between a closed positionto close off the fluid conveying channel from the reaction chamber andan open position to allow fluid to flow from the fluid conveying channelinto the reaction chamber.

In accordance with another aspect of the invention, a method ofconducting an in-vitro diagnostic test is provided. The method includesproviding a body configured to be hand held having a reaction mediumsupply chamber with a reaction fluid contained therein in selectivefluid communication with a thermal reaction medium contained in areaction chamber via a fluid conveying channel wherein the reactionchamber is beneath a sample reaction chamber; disposing a sample in thesample reaction chamber; and dispensing a reaction fluid from thereaction medium supply chamber into the reaction chamber and producingone of an endothermic or exothermic reaction within the reaction chamberbeneath the sample reaction chamber.

In accordance with another aspect of the invention, the method furtherincludes depressing a bulb and causing the reaction fluid to rupture amembrane and flow into the reaction chamber.

In accordance with another aspect of the invention, the method furtherincludes causing a self-actuable valve to move between open and closedpositions to respectively allow and prevent the flow of the reactionfluid into the reaction chamber in response to the endothermic orexothermic reaction.

In accordance with another aspect of the invention, the method furtherincludes causing the self-actuable valve to move between the open andclosed positions by buffering a portion of the thermal reaction medium.

In accordance with another aspect of the invention, the method furtherincludes reacting water with CuSO4 to produce an exothermic reaction.

In accordance with another aspect of the invention, the method furtherincludes reacting oxygen with iron to produce an exothermic reaction.

In accordance with another aspect of the invention, the method furtherincludes reacting citric acid with sodium bicarbonate to produce anendothermic reaction.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects, features and advantages of the invention willbecome more readily appreciated when considered in connection with thefollowing detailed description of presently preferred embodiments andbest mode, appended claims and accompanying drawings, in which:

FIG. 1 illustrates an example of a typical thermal cycle profile used ina denaturing and replication process of DNA;

FIG. 2 illustrates a perspective view of an exothermic or endothermicreaction member constructed in accordance with one aspect of theinvention;

FIG. 3A illustrates a partial cross-sectional view of an exothermic orendothermic reaction member constructed in accordance with anotheraspect of the invention;

FIGS. 3B-3C illustrate cross-sectional views of an exothermic orendothermic reaction members constructed in accordance with furtheraspects of the invention;

FIGS. 4A-4B illustrate respective cross-sectional plan and perspectiveviews of a deactivated disposable in-vitro diagnostic apparatusconstructed in accordance with one aspect of the invention utilizing anexothermic or endothermic reaction member of FIG. 2;

FIG. 5A illustrates the apparatus of FIGS. 4A-4B in an activated state;

FIG. 5B is a view similar to FIG. 5A illustrating a disposable in-vitrodiagnostic apparatus constructed in accordance with another aspect ofthe invention utilizing exothermic or endothermic reaction members of atleast one of FIGS. 3A-3C;

FIG. 6 is a perspective view of thermal transfer mechanism constructedin accordance with another aspect of the invention in combination withan exothermic or endothermic reaction member;

FIGS. 7A-7C illustrate various states of a thermal control mechanismconstructed in accordance with another aspect of the invention forregulating the thermal energy in an apparatus constructed in accordancewith another aspect of the invention;

FIG. 8A illustrates a portion of a disposable in-vitro diagnosticapparatus constructed in accordance with the invention incorporating thethermal control mechanism of FIGS. 7A-7C with the thermal controlmechanism shown in a maximum thermal energy conveying conduction statecorresponding to FIG. 7B;

FIG. 8B shows the apparatus of FIG. 8A with the thermal controlmechanism shown in a minimum thermal energy conveying convection statecorresponding to FIG. 7C;

FIGS. 9A-9C illustrate a valve for regulating the flow of a reactant ina disposable in-vitro diagnostic apparatus constructed in accordancewith another aspect of the invention;

FIGS. 10A-10B illustrate a disposable in-vitro diagnostic apparatusincorporating the valve of FIGS. 9A-9B with the valve being shown inrespective open and closed states;

FIG. 11A illustrates a perspective view of a fluid activation system ofa disposable in-vitro diagnostic apparatus constructed in accordancewith another aspect of the invention;

FIG. 11B is a cross-sectional plan view of the apparatus of claim 11A;

FIG. 12A illustrates an exploded perspective view of a disposablein-vitro diagnostic apparatus constructed in accordance with yet anotheraspect of the invention;

FIG. 12B illustrates the apparatus of FIG. 12A in combination with anexternal energy supply device;

FIG. 13A is a schematic of energy supply device for use on a disposablein-vitro diagnostic apparatus constructed in accordance with anotheraspect of the invention; and

FIG. 13B is exploded perspective view of a disposable in-vitrodiagnostic apparatus constructed in accordance with yet another aspectof the invention including the energy supply device of FIG. 13A.

DETAILED DESCRIPTION OF PRESENTLY PREFERRED EMBODIMENTS

Referring in more detail to the drawings, disposable in-vitro diagnosticapparatus, referred to hereafter as apparatus 10, constructed inaccordance with various presently preferred embodiments of the inventionare illustrated, by way of example and without limitation. The apparatus10 provide a quick, reliable and economical method for performing athermally activated in-vitro diagnostic test on a selected specimen. Theapparatus 10 is both economical in manufacture and in use, is readilyportable, such that it is sized to be hand held for single use,whereupon the apparatus 10 is disposable after use, particularly giventhe low cost associated with its manufacture. The apparatus 10 can beprovided as an all inclusive device, including an integral exothermicreaction heat producing or endothermic heat reducing and regulatingmechanism, or it can be configured for operable electrical connection toa separate energy source to power a thermal reaction within theapparatus (FIGS. 12A-12B). If configured for operable attachment to aseparate energy source, the energy source and/or the apparatus 10 can beconfigured to regulate the thermodynamics within the apparatus 10, asdiscussed further below.

The heat production via the exothermic chemical reaction or heatreduction via the endothermic reaction may be achieved by combining twoor more elements or chemical substances, known as reactants, providedand contained entirely and integrally within the apparatus 10. Thecombination of the reactants produces a product and a release of energyor a reduction of energy from the surrounding environment. The change inenthalpy, (thermodynamic potential) for an exothermic reaction is lessthan zero (<0), and thus, a larger value of energy released in thereaction is subtracted from a smaller value of energy used to initiatethe reaction, the opposite being true for an endothermic reaction.

The exothermic reactants may be provided individually as, or as acombination of, solids, liquids and gasses. Some examples include:

Combining anhydrous copper (II) sulfate with water (Solid+Liquid):CuSO₄+5H₂O→CuS₄·5H₂O+HEAT; or

Combining oxygen with iron (Gas+Liquid):4Fe+3O₂→2Fe₂O₃+HEAT.

The endothermic reactants may be provided individually as, or as acombination of, solids, liquids and gasses. Some examples include:

Combining citric acid and sodium bicarbonate:H₃C₆H₅O₇(aq)+3NaHCO₃(s)→3CO₂(g)+3H₂O(l)+Na₃C₆H₅O₇(aq).

Additionally, as shown in FIG. 6, heat or cooling can be generatedremotely from the sample being heated or cooled. Remote transport ofthermal energy is provided by conduction through a material of highthermal conductivity, expressed in units of power per distancemultiplied by temperature; W/m·K or W/m ° C., Btu/(hr ° F. ft²/ft).Remote heat transfer provides distribution of the thermal energythroughout the disposable device to locations desired, and also providesa source of varying temperature gradient to one or more points.

In accordance with one aspect of the invention, as shown in FIGS. 7-9,the apparatus 10 can include a thermal cycling mechanism 12 to regulateand vary the heat or subtraction of energy transferred to or from to thesample. The thermal cycling mechanism 12 can be configured via amulti-layered composite, producing a thermal cycle based on the rate ofreaction, quantity of reactants present and desired thermal cyclingfrequency. As the exothermal or endothermal reaction progresses, theheat or cooling produced by the chemical reaction may be regulated bythe thermal regulating mechanism 12, which can include a valve member13, such as a bimetallic member, located between the thermal source andthe sample being heated or cooled. The bimetallic member 13 is designedto move between an actuated and non-actuated position at predeterminedtemperatures, thus, providing an automated temperature regulation and athermal cycling profile. This function can be applied to the abovedescribed remote thermal transport element (FIG. 6) and to an electricalthermal energy control by acting as an electric switch (FIGS. 12 and13).

As shown in FIGS. 9A-9C, thermal cycling within the apparatus 10 can beprovided via a bimetallic, thermally actuated valve 14, which, at apredetermined temperature, changes from concave (FIG. 9A) to convex(FIG. 9B) with respect to a valve port 16. Upon heating or cooling tothe predetermined actuation temperature, the valve 14 moves to a closedconvex configuration (FIG. 9B), thus closing off flow of the reactantthrough the valve port 16, and upon cooling the valve 14 moves to anopen concave configuration (FIGS. 9A and 9C), thus restoring the flow ofthe reactant through the valve port 16. The mechanical threshold ofactuation results in a “snapping action” upon the valve member 13“crossing over center”.

As shown in FIGS. 12A-13B, in addition to, or in lieu of producing heatvia a chemical reaction mechanism within the apparatus 10, heat may begenerated by placement of an electrical heating element 18 proximal tothe sample being heated. The heating element 18 may be actuated by anenergy source 20, such as a DC battery, by way of example, locatedintegrally within the disposable apparatus 10 (FIG. 13A-13B), or from aseparate energy source 20 external to the apparatus 10, such as a DCbattery, by way of example, which is configured to interfaceelectrically with the disposable device (FIGS. 12A-12B).

An electrical switch can be provided by a manual switch or by alow-level resistive or capacitance switch via contact with the samplefluid and coupled with a transistor on the apparatus 10. Furthermore, atemperature reactive bimetallic switch may be employed, proximal to thefluid sample, such as discussed with regard to FIGS. 7A-7C, to regulatethe temperature, or to produce a thermal cycling profile.

As shown in FIGS. 11A-11B, the fluid reactant channeled to promote thethermal reaction may be introduced to the reaction chamber by a wickmember 22, and/or a controlled capillary channel. This mechanism andmethod of channeling the reactant can be configured to regulate the rateof fluid transfer as desired, thereby allowing the heat or coolinggenerated to be controlled, as desired. One or more fluid blisters 24containing the fluid reactant F, or other sources of reactant, areprovided to initiate the thermal reaction cycle. Additionally, fluidreactants having different reactivity can be provided via the differentsources of reactant, which provide a mechanism and method for varyingthermal profiles. The sequential introduction of the fluid reactants atprescribed time intervals further facilitate regulating the thermalprofile and timing thereof.

In FIG. 2, an exothermic multi-layered composite medium, shown as a diskstack 26 of alternating exothermic values, is illustrated in accordancewith one aspect of the invention. As the reaction progresses, thequantitative level of exothermic energy produced alternates inaccordance to the desired thermal output level, thus, achieving thedesired thermal cycle. The outer peripheral sides of the stack 26 can beshielded from the chemical reactant, such as by an inert coating, notsubject to dissolution upon exposure to the reactive fluid. Theexothermal reactant chemical discussed above, CuSO4 is provided as anexample, and thus, it should be recognized that additional endothermicand exothermic reactive solids could be used.

In FIG. 3A, an exothermal or endothermal composite medium, shown as abead or sphere 28, is illustrated in accordance with another aspect ofthe invention, which is a derivation of the exothermic composite diskstack 26, with the primary difference of surface area and the number ofindividual points of reaction. A plurality of the composite spheres 28provides an increased outer reactive surface area, and thus, provides amore intense reaction. The plurality of reactive spheres 28 can beprovided in a predetermined configuration and quantity to produce thedesired thermal cycling effect.

In FIG. 3B-3C, exothermal or endothermal composite beads or spheres 30are illustrated in accordance with another aspect of the invention. Theexothermal or endothermal spheres 30 are similar to the previouslydiscussed composite beads or spheres 28 of FIG. 3A, however, they arebuffered with a coating 32. The buffered coating 32 provides atimed-release of the active agent 34 in the exothermic reaction.Reactive spheres 30 having differing buffers 32 and thicknesses ofbuffer 32 (FIG. 3B being thicker than FIG. 3C) result in a stagedthermal cycle, as desired. A further difference with the bufferedexothermal or endothermal composite spheres 30 over the spheres 28 ofFIG. 3A is that the buffered spheres 30 of FIGS. 3B-3C each consist ofonly one reactive element 34 internal to the buffered coating 32.

In FIGS. 4A-4B, an apparatus 10, constructed in accordance with oneaspect of the invention, includes a unitized housing or body 11 sized tobe hand held, and thus, the body 11 is readily carried in a palm of ahand. The body 11 can be constructed of any suitable materials,preferably relatively inexpensive moldable polymeric materials. The body11 carries and provides the components of the apparatus 10 as aunitized, portable and disposable assembly. In accordance with oneaspect of the invention, the body 11 carries an exothermal orendothermal composite series of plates or disks 26, also referred to asa “reaction” stack, such as discussed and shown in FIG. 2, residingunder a sample reaction chamber 36. The chamber 36 is separated from thethermal reaction stack 26 by a thermally conductive barrier 38, thusisolating the byproducts of the thermal reaction from the sample 40being heated or cooled. A self-contained reactive fluid F isencapsulated and contained in a flexible and sealed elastic bulb orblister, also referred to as a reaction fluid supply chamber 24, shownas a “blister pack”, that is in selective fluid communication with thethermal reaction medium or stack 26 contained in a reaction chamber 50via a fluid conveying channel 42, and to a distal (downstream of thesample 40) waste/overflow chamber 44, which is vented to atmosphere oranother chamber. The sample chamber 36 may be covered and seal off by anoptically clear cover window 46 to permit visual or optical analysis ofthe reaction within the chamber 36.

As best shown in FIGS. 5A-5B, the blister 24 containing the reactivefluid F is depressed via an externally applied force, such as bymanually depressing the blister 24 with a thumb or finger, for example,thereby causing the reactive fluid to selectively rupture a membrane 48closing off the channel 42. Upon the membrane 48 being ruptured, thefluid passes through the channel 42 to the reaction chamber 50containing the thermal reaction stack 26. The stack 26 reacts with thereactive fluid F, thereby producing an endothermic or exothermic releaseof energy. The thermally conductive barrier 38 conducts or removes thethermal energy to or from the sample 40 being heated or cooled. Excessfluid travels to the waste/overflow chamber 44, and the gases producedby the reaction are vented via a hydrophobic membrane 52, thus balancingthe pressures present within the disposable apparatus 10. FIG. 5B issimilar to FIG. 5A, however, it incorporates at least one or more typesof the exothermal or endothermal reactive beads or spheres 28, 30discussed above and shown in FIGS. 3A-3C. As with FIG. 5A, the reactionis vented, thus balancing the pressures present within the disposableapparatus 10.

FIG. 6 depicts the use of a thermal conductor 54 to transfer the thermalenergy to or from the point of an assay reaction. This allows remotegeneration of energy, thus, multiple sources of energy may be directedto a single point or location. The figure discussed above represent onlya single location of energy.

FIG. 7A depicts the thermally cycling mechanism in the form of adeformable bimetallic or shape memory alloy disk 12. The objective ofthis component is to regulate the level of thermal energy extended to orfrom the assay chamber 36. The thermal barriers 38 shown in FIGS. 4A-4Band 5A-5B can be provided as such, such as via a bimetallic, shapememory alloy or other thermally deformable material, thus allowing forthe thermal barrier 12 to automatically change its configuration at aprescribed temperature. The deformable thermal barrier 12 is in contactwith the thermally conductive member 38 prior to the thermal reaction.The bias shape of FIG. 7B provides positive physical abutment of thethermal barrier 12 with the thermally conductive member 38 upon assemblyof the thermal barrier 12 and prior to heating or cooling. It should berecognized that the thermal barrier 12 can be constructed having anydesired shape.

FIG. 7C depicts the thermally deformable, or shape memory alloy barrier12, deflected at a prescribed temperature, lifting off of the thermallyconductive member 38, thus limiting the conduction of energy from thethermal reaction chamber 50 via an insulation gap G. The naturalresonate frequency governing the period between deflection andnon-deflection is a function of design and temperature. This frequencyresults in the desired thermal cycling between the configurations shownin FIGS. 7B and 7C.

FIG. 8A illustrates an apparatus 10 including the thermally deformablebarrier 12 of FIGS. 7A-7C, in the un-actuated state. While, in itsun-actuated state, thermal energy resulting from a combination of thefluid reactant F and the exothermal or endothermal composite medium isconducted through the thermally conductive barrier 38 and through thethermally deformable barrier 12.

FIG. 8B depicts the thermally deformable barrier 12 deflected (actuated)at a prescribed temperature to provide the gap G, thus limiting theconduction of energy from the thermal reaction chamber 50 to the samplechamber 36. Upon reaching a designed target temperature, the thermallydeformable barrier 12 looses physical conduct with the thermallyconductive barrier 38, thus eliminating conduction of heat or coolingfrom the reaction chamber 50 to the sample chamber 36. The thermallydeformed material 12 returns to its physically conductive position (FIG.8A) upon cooling. The cooling process occurs due to the lack of physicalcontact with the heated or cooled conduction surface 38.

FIGS. 9A-9B depict the valve 14 comprised of a thermally deformable orshape memory alloy device 13, capable of deflecting at a prescribedtemperature, thus regulating the flow of reaction fluid F to thereaction chamber 50. In FIG. 9A the valve 14 is shown in the openposition, wherein the fluid F is able to flow to the reaction chamber50. A thermal conductor 54, as described and shown in FIG. 6, may beadapted to this design to allow control of the valve 14 from a remotelocation. This valve 14 would also produce a thermal cycling, uponopening and closing, to regulate a thermal reaction.

FIG. 9B depicts the valve 14 in the closed position, thereby preventingthe flow of the fluid reactant F to the reaction chamber 50. As such,the thermal reaction “down-stream” of the valve 14 is impeded, thusreducing the thermal energy the valve 14 is exposed to, resulting in areopening of the valve 14.

FIG. 9C depicts a thermally deformable shape memory valve 14 withelectrical contacts 56 for electrical actuation. Nitinol, a common shapememory alloy undergoes elastic deformation upon thermal or electricalexposure. The valve 14 deflects upon passing current through the valve14.

FIG. 10A illustrates an apparatus 10 incorporating the valve 14 in FIGS.9A-9C, and also the thermally deformable member 12 described in FIGS.7A-8B. The valve 14 is shown in the open position, permitting flow ofthe liquid reaction agent F to the solid reactant. FIG. 10B depicts theintegrated thermal valve 14 in the closed position, thus inhibiting theflow of the liquid reaction agent into fluid contact with the solidreactant 26.

FIG. 11A depicts a device for introducing the reaction fluid into thereaction chamber remotely via the wick member 22. The wick 22 regulatesthe flow of the reaction fluid into the reaction chamber 50, thusregulating the rate of the reaction. The wick 22 can be provided havingany desired cross-sectional shape along its length, and further, can beformed from any desired wicking material, thereby allowing the flow rateof wicking of the reaction fluid to be precisely controlled.

FIG. 11B is a cross-section of an apparatus 10 incorporating the remotefluid wicking device 22 of FIG. 11A.

FIG. 12A depicts a disposable apparatus 10 constructed in accordancewith another aspect of the invention including the embedded thermalelement 18 and electrical contacts 58 for interface with the electricalenergy source 20. The thermal element 18 includes a resistive element 60embedded in the reaction chamber 50. The external energy source 20provides the current to heat the resistive elements 60.

FIG. 12B shows the apparatus 10 in FIG. 12A interfacing with an externalenergy source 20. The energy source 20 is capable of producing an energyprofile, which in turn, produces the desired thermal profile. A simplecircuit may provide for intermittent, or cycling of the energy source20, resulting in a thermal cycling profile in the reaction chamber 50.

FIG. 13A is a schematic of a “on-device”, battery powered heatingelement, with a simple transistor relay. The transistor receives itssignal from a pair of contacts embedded in the reaction chamber 50 whichare “connected” upon contact with the fluid sample being heated. Thefluid sample provides and electrical path between the contacts, thuscompleting the circuit. The addition of a thermal switch would provide athermal cycling profile.

FIG. 13B depicts an embodiment of the schematic in FIG. 13A in adisposable apparatus 10. The switching transistor provides the means toturn on and of the heating element, and when coupled with one of thethermally cycling devices describe prior, may also yield the thermalcycling profile.

What is claimed is:
 1. A method of conducting an in-vitro diagnostictest, comprising: providing a body configured to be hand held having areaction medium supply chamber with a reaction fluid contained thereinin selective fluid communication with a thermal reaction mediumcontained in a reaction chamber via a fluid conveying channel whereinthe reaction chamber is beneath a sample reaction chamber; disposing asample in the sample reaction chamber; dispensing a reaction fluid fromthe reaction medium supply chamber into the reaction chamber andproducing one of an endothermic or exothermic reaction within thereaction chamber beneath the sample reaction chamber; and furtherincluding causing a self-actuable valve within the body to automaticallymove between open and closed positions in response to thermal energyacting on the self-actuable valve to regulate the flow of the reactionfluid into the reaction chamber.
 2. The method of claim 1 furtherincluding depressing a bulb and causing the reaction fluid to rupture amembrane and flow into the reaction chamber.
 3. The method of claim 1further including producing an exothermic reaction.
 4. The method ofclaim 3 further including reacting water with CuSO4 to produce theexothermic reaction.
 5. The method of claim 3 further including causingthe self-actuable valve to move between the open and closed positions bybuffering a portion of the thermal reaction medium.
 6. The method ofclaim 1 further including producing an endothermic reaction.
 7. Themethod of claim 1 further including connecting the body to an externalpower source.